Iodine-Mediated Intramolecular Dehydrogenative Coupling: Synthesis of N-Alkylindolo[3,2-c]- and -[2,3-c]quinoline Iodides

Abstract

An I2/TBHP-mediated intramolecular dehydrogenative coupling reaction is developed for the synthesis of a library of medicinally important 5,11-dialkylindolo[3,2-c]quinoline salts and 5,7-dimethylindolo[2,3-c]quinoline salts. The annulation reaction is followed by aromatization to yield tetracycles in good yield. This protocol is also demonstrated for the synthesis of the naturally occurring isocryptolepine in salt form.

Isolation and synthesis of cryptosanguinolentine (isocryptolepine), a naturally-occurring bioactive indoloquinoline alkaloid

“…More recently, 26 was accessed by Volvoikar and Tilve in 75% yield from 25, employing a cross-dehydrogenative coupling reaction with TBHP and I 2 . 53 The mechanism of the transformation of the hydrazone intermediate 18 into the tetracycle 1 is depicted in Scheme 6. It is proposed that the protonation of 18 to afford A would give B aer tautomerization.…”

Metal‐Free Cross‐Dehydrogenative Coupling (CDC): Molecular Iodine as a Versatile Catalyst/Reagent for CDC Reactions

“…Indolo[3,2‐ c ]quinolines and indolo[2,3‐ c ]quinolines have been synthesized from 2‐( N , N ‐dimethylaniline)‐substituted indoles and 3‐( N , N ‐dimethylaniline)‐substituted indoles, respectively, through intramolecular dehydrogenative coupling (Scheme ) . Electron‐neutral and electron‐rich groups on the indole ring are well tolerated, and the products are obtained in good yields.…”

Highly Efficient Construction of Pentacyclic Carboline‐Containing Salts via a [Cp*RhCl2]2‐Catalyzed Tandem Reaction

“…Sempervirine, which structure was elucidated and synthesized by Woodward, was found to be a potential antitumor agent. [6] However, these exiting strategies often required multistep synthesis, suffering from a lot of shortcomings such as long production time, low overall yields of the desired products and massive effort for the isolation and purification of intermediates. [4] Indolo [2,3-b]salt was reported to be an efficient intercalator with DNA-Photodamaging properties.…”